Published online before print January 31, 2002, doi: 10.1161/hh0402.105956
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Submitted on March 7, 2001
Revised on January 17, 2002
Accepted on January 17, 2002
Targeting CCR2 or CD18 Inhibits Experimental In-Stent Restenosis in Primates. Inhibitory Potential Depends on Type of Injury and Leukocytes Targeted
Christopher Horvath ;
From the Department of Medicine, Cardiac Catheterization Laboratory, Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Mass and the Harvard/MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, Mass (F.G.P.W., C.R.); the West Roxbury Veteran's Affairs Medical Center (F.G.P.W.), West Roxbury, Mass; and the Clinical Investigator Training Program, Harvard/MIT Division of Health Sciences and Technology-Beth Israel Deaconess Medical Center, in collaboration with Pfizer Inc (F.G.P.W.), Millennium Pharmaceuticals (C.H., P.R.), Cambridge, Mass, and Primedica Corporation (M.N.), Worcester, Mass.
* To whom correspondence should be addressed. E-mail: welt{at}mediaone.net.
A central role for leukocytes in neointimal hyperplasia after arterial injury is suspected. However, the relative importance of neutrophils and monocytes in balloon or stent-induced injury are not well understood, and mechanistic targeting of leukocyte recruitment or function is crude. We determined the temporal and spatial distribution of different leukocytes after balloon and stent-induced injury in primate iliac arteries. Based on these data, we targeted neutrophil and monocyte recruitment selectively after angioplasty or stent implantation and demonstrated that monocyte-specific blockade achieved via blockade of the MCP-1 receptor CCR2, was effective at reducing neointimal hyperplasia after stenting. In contrast, combined neutrophil and monocyte blockade achieved by targeting the leukocyte ß2-integrin ß-subunit CD18 was required to reduce neointimal hyperplasia after balloon injury. Distinct patterns of leukocyte infiltration in balloon versus stent-injured arteries predict distinct mechanisms for antiinflammatory strategies targeting neutrophils or monocytes in primates and may assist design of effective clinical strategies for optimizing vascular interventions.
Key words: stents • leukocytes • primates
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